Plasma long noncoding RNA expression profile identified by microarray in patients with Crohn's disease

World J Gastroenterol. 2016 May 21;22(19):4716-31. doi: 10.3748/wjg.v22.i19.4716.

Abstract

Aim: To investigate the expression pattern of plasma long noncoding RNAs (lncRNAs) in Chrohn's disease (CD) patients.

Methods: Microarray screening and qRT-PCR verification of lncRNAs and mRNAs were performed in CD and control subjects, followed by hierarchy clustering, GO and KEGG pathway analyses. Significantly dysregulated lncRNAs were categorized into subgroups of antisense lncRNAs, enhancer lncRNAs and lincRNAs. To predict the regulatory effect of lncRNAs on mRNAs, a CNC network analysis was performed and cross linked with significantly changed lncRNAs. The overlapping lncRNAs were randomly selected and verified by qRT-PCR in a larger cohort.

Results: Initially, there were 1211 up-regulated and 777 down-regulated lncRNAs as well as 1020 up-regulated and 953 down-regulated mRNAs after microarray analysis; a heat map based on these results showed good categorization into the CD and control groups. GUSBP2 and AF113016 had the highest fold change of the up- and down-regulated lncRNAs, whereas TBC1D17 and CCL3L3 had the highest fold change of the up- and down-regulated mRNAs. Six (SNX1, CYFIP2, CD6, CMTM8, STAT4 and IGFBP7) of 10 mRNAs and 8 (NR_033913, NR_038218, NR_036512, NR_049759, NR_033951, NR_045408, NR_038377 and NR_039976) of 14 lncRNAs showed the same change trends on the microarray and qRT-PCR results with statistical significance. Based on the qRT-PCR verified mRNAs, 1358 potential lncRNAs with 2697 positive correlations and 2287 negative correlations were predicted by the CNC network.

Conclusion: The plasma lncRNAs profiles provide preliminary data for the non-invasive diagnosis of CD and a resource for further specific lncRNA-mRNA pathway exploration.

Keywords: Crohn’s disease; Inflammatory bowel disease; Long noncoding RNA; Microarray; Plasma.

MeSH terms

  • Adult
  • Case-Control Studies
  • Computational Biology
  • Crohn Disease / blood*
  • Crohn Disease / diagnosis
  • Crohn Disease / genetics
  • Female
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Genetic Markers
  • Humans
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis*
  • RNA, Long Noncoding / blood*
  • RNA, Long Noncoding / genetics
  • Real-Time Polymerase Chain Reaction

Substances

  • Genetic Markers
  • RNA, Long Noncoding